Document text
1
JULY MONTHLY MEETING SUMMARY
Application number: BLA STN 125742/0
Product name: COVID- 19 mRNA Vaccine (COMIRNATY)
Proposed Indication: Active immunization to prevent COVID -19 caused by SARS -
CoV- 2 in individuals 16 years of age and older
Applicant: BioNTech Manufacturing GmbH
Meeting date & time: July 15 , 2021; 3:30 - 5:00 PM EDT
Committee Chair: Ramachandra Naik, Ph.D.
Meeting Recorder s: CAPT Michael Smith, Ph.D. and
Laura Gottschalk, Ph.D.
1. Background
This meeting was to discuss the original BLA (STN 125742/0) from BioNTech
Manufacturing GmbH (in partnership with Pfizer, Inc.) for COVID -19 mRNA Vaccine , for
active immunization to prevent COVID -19 caused by SARS -CoV- 2 in individuals
16 years of age and older . This is a Rolling BLA submission. The first roll containing
eCTD sections 2, 4, and 5 was submitted and received on May 6, 2021. The second and
final roll containing eCTD Section 3 (and the rest of Section 1 items) was submitted and
received on May 18 , 2021.
The purpose of this meeting was to discuss the progress of the review, identify and
present any issues, and plan the remainder of the review, including dates for further deliverables and interactions.
Table 1: Review Committee (attendees are listed in bold font)
Review responsibility Committee Member Team Leader / Supervisor(s) Division Director
Chairperson Ramachandra Naik, PhD BC: Elizabeth Sutkowski , PhD DD: Loris McVittie , PhD
SA: Kirk Prutzman , PhD (acting)
Regulatory Project
Managers CAPT Mike Smith , PhD
Laura Gottschalk , PhD BC: Elizabeth Sutkowski , PhD DD: Loris McVittie , PhD
SA: Kirk Prutzman , PhD (acting)
Clinical Susan Wollersheim , MD
CAPT Ann Schwartz , MD TL: Lucia Lee , MD
BC: Maria Allende , MD DD: Doran Fink , MD, PhD
Product (CMC)
DVP Reg coordinator,
DVP Product Specialist Xiao Wang , PhD
Anissa Cheung , MSc BC: Keith Peden , PhD DD: Jerry Weir , PhD
DDD: Robin Levis , PhD
DS and DP release assays
DS and DP release assays
DS and DP release assays
DS and DP release assays
DS and DP release assays
LRP and Testing Plan Dev. Hsiaoling Wang , PhD
Emnet Yitbarek, PhD Karla Garcia, MS
Anil Choudhary, PhD, MBA
Esmeralda Alvarado , PhD
Marie Anderson , PhD TL: Tao Pan , PhD
TL: Tao Pan , PhD
BC: CDR James Kenney, DSc
BC: Muhammad Shahabuddin , PhD
BC: Muhammad Shahabuddin , PhD
Maryna Eichelberger , PhD DD: Maryna Eichelberger , PhD
DDD: N/A
FDA-CBER-2021-5683-1024843
STN 1 25742/0 Monthly Meeting date: July 15, 2021
2
Review responsibility Committee Member Team Leader / Supervisor(s) Division Director
Toxicology Nabil Al -Humadi, PhD BC: Martin Green , PhD DD: Doran Fink , MD, PhD
Statistics :
Efficacy data
Safety data
Non-clinical data
Lei Huang , PhD
Ye Yang , PhD
Xinyu Tang , PhD
BC: Tsai-Lien Lin , PhD
TL: Lei Huang , PhD
BC: Tsai-Lien Lin , PhD DD: John Scott, PhD
DDD: Shiowjen Lee, PhD
Epidemiology/
Pharmacovigilance Deborah Thompson , MD,
MSPH TL: LCDR Jane Baumblatt, MD
BC: Manette Niu , MD DD: Narayan Nair, MD
DDD: Meghna Alimchandani, MD
DMPQ Reviewer/Inspector
DMPQ Reviewer/Inspector
DMPQ Reviewer
DMPQ Inspector
DMPQ Inspector
DMPQ Inspector
Lot Release
DMPQ RPM Kathleen Jones , PhD
Laura Fontan , PhD
Gregory Price , PhD
Zhongren Wu, PhD
CDR Donald Ertel , MS
Ekaterina Allen , PhD
Cheryl Hulme
Iryna Zubkova, PhD TL: Nicole Li
BC: Lori Peters, MS TL: CDR Donald Ertel , MS
BC: Lori Peters, MS
BC: Anthony Lorenzo
BC: Joseph Quander
BC: James Crim DD: John Eltermann , RPh, MS
DDD: Carolyn Renshaw
BIMO Haecin Chun ,
MT(ASCP)SBB, MS BC: Dennis Cato DD: Carrie Mampilly , MPH
APLB Labeling
reviewer CAPT Oluchi Elekwachi ,
PharmD, MPH
Dana Jones BC: Lisa Stockbridge , PhD DD: Robert Sausville
Container Labeling Daphne Stewart BC: Timothy Nelle, PhD DD: Loris McVittie , PhD
Electronic integrity CDR David Schwab, MSIS Loris McVittie , PhD DD: Loris McVittie , PhD
CDISC consult Brenda Baldwin , PhD
Kirk Prutzman , PhD BC: Elizabeth Sutkowski , PhD DD: Loris McVittie , PhD
Other Attendees:
Sudhakar Agnihothram, Nicolette Devore, Varsha Garnepudi, Marion Gruber , Maureen Hess ,
Douglas Pratt, Philip Krause, David Rouse and Leslie Taylor
Review Timetable ( PDUFA Milestones are in blue)
Review Milestone Target Due Date
Submitted
Roll 1 Submission: 06-MAY- 2021
Roll 2 Submission (final): 18-MAY- 2021
Received: 18-MAY- 2021
Committee Assignment: 09-JUN- 2021
First Committee Meeting: 03-JUN- 2021
Filing checklist/reviews complete: 23-JUN- 2021
Filing Meeting: 29-JUN- 2021
Filing Action: 16-JUL-2021
Deficiencies Identified:
31-JUL-2021
Initial proprietary name review: 16-AUG -2021
Primary Draft Reviews & Reviewer Reports Due
(4 days prior to Mid- Cycle meeting): 25-AUG -2021
Mid-Cycle Meeting (Internal): 31-AUG -2021
Mid-Cycle Communication: 13-SEP- 2021
Final draft primary reviews with supervisory Concurrence (upload not required) : 01-SEP- 2021
FDA-CBER-2021-5683-1024844
STN 1 25742/0 Monthly Meeting date: July 15, 2021
3
PLI Inspections completed: 30-JUL-2021
BiMO Inspections completed: 30-JUL-2021
PeRC briefing materials due to PeRC: 27- JUL-2021
PeRC Meeting: 10-AUG -2021
Lot release protocol & testing plan finalized: 15-AUG -2021
Notify OCOD of pending approval: 15-AUG -2021
Draft SBRA 15-AUG -2021
Labeling Comments to Applicant: 15-AUG -2021
Notify Applicant of PMC/PMR: 15-AUG -2021
Final reviews & addenda signed & uploaded: 30-AUG -2021
Targeted Action Due Date (ADD) 15-SEP- 2021
PDUFA ADD: 16-JAN-2022
Table 2: Scheduled Meetings (new meetings in italics)
PDUFA Meetings:
• First Committee Meeting: June 3, 2021, 4:00PM – 5:30PM
• Filing Meeting: June 29, 2021, 2:00PM – 3:30PM
• Internal Mid -Cycle: August 31, 2021, 2:00PM – 3:30PM
• Mid-Cycle Communication: September 13, 2021, 3:00PM – 4:00PM
Monthly Committee Meetings:
• July 15, 2021, 3:30PM – 5:00PM
• August 9, 2021, 1:30PM – 3:00PM
• September 10, 2021, 12:30PM – 2:00PM
Labeling Meetings:
• August 4, 2021, 3:00PM – 5:00PM
• August 6, 2021, 3:00PM – 5:00PM
• August 11, 2021, 3:00PM – 5:00PM
• August 16, 2021, 11:00AM – 12:30PM (Carton & Container)
• August 18, 2021, 3:30PM – 5:00PM (Carton & Container)
• August 23, 2021, 4:00PM – 5:30PM
• August 25, 2021, 2:30PM – 4:30PM
• September 2, 2021, 4:00PM – 5:30PM
• September 7, 2021, 2:00PM – 4:00PM
• September 21, 2021, 3:00PM – 5:00PM
Other Meetings:
• June 4, 2021, 12:30 – 1:30 PM (Testing to support licensure; DVP and
DBSQC)
• July 26, 2021, 3:00 – 4:00 PM (Discussion of non -proprietary name )
FDA-CBER-2021-5683-1024845
STN 1 25742/0 Monthly Meeting date: July 15, 2021
4
2. Discussion Topics
2.1 Opening remarks from the Chair and RPMs
• As noted in the email sent to the review team on July 9, 2021, the new
targeted action due date (ADD) for the BLA is September 15, 2021.
• Prior to the meeting, the Chair requested that the review committee provide
projected dates for the completion of their discipline review s. Please see
Table 3, included at the end of this document , for a list of review activities and
projected target completion dates (Appendix).
• The RPMs summarized the IRs and Amendments to the BLA to date (please
see details at end of document).
2.2 Review of milestones and internal/projected target dates
• The Filing Letter is targeted to be issued and sent to the Applicant on July 16,
2021.
• A meeting to discuss the non- proprietary product name has been scheduled
for July 26, 2021.
2.3 Status update (including any major concerns that have been identified so far) from each member of the review committee
2.3.1 Clinical (Susan Wollersheim and Ann Schwartz):
• The clinical reviewer s have been working with the statistical reviewers to
determine the preferred terms for AESIs in the VAERS datasets so that
they correlate with safety analysis in clinical trials . They are currently
ensuring that no IRs will be required for the unblinded periods of the
clinical trials. Additionally, IRs regarding efficacy of the vaccine are being
drafted regarding the inclusion of data from subjects 12-15 years of age
and to provide shell tables to the Applicant for safety and efficacy .
2.3.2 CMC (Xiao Wang):
• The CMC reviewer sta ted that the r eview of the drug substance is close
to be finished which will then be follo wed by review of the drug product.
There were no specific issues that needed to be discussed with the
group during the meeting.
2.3.3 DBSQC (Hsiaoling Wang, Emnet Yitbarek, Karla Garcia, Anil Choudhary, Esmeralda Alvarado and Marie Anderson):
• The DBSQC reviewers provided updates that the reagents and lots for
testing were received last week. IRs regarding the lot release protocol
templates as well as the number of freeze/thaws allowed for the drug substance will be finalized for sending to the Applicant soon.
• It is not certain at this time that t he in-support testing (
of DS) will be complete by the target action date since
(b) (4)
FDA-CBER-2021-5683-1024846
STN 1 25742/0 Monthly Meeting date: July 15, 2021
5
some of the reagents required for testing have been backordered and
the new equipment need to be installed.
2.3.4 Toxicology (Nabil Al -Humadi):
• The toxicology reviewer w as unable to attend the meeting, but there
were no issues to be discussed regarding the progress of the toxicology
review.
2.3.5 Statistics (Lei Huang , Ye Yang and Xinyu Tang):
• The statistical reviewer noted that his review is ongoing and they are
targeting completion of the stats review memo at the same time as the
completion of the clinical review. To help with the review, two new
statistical reviewers have been added to the review committee: Ye Yang will review safety data while Xinyu Tang will be responsible for non -
clinical data. Xinyu Tang asked to contact her if any of the discipline
reviewers need non- clinical stats support.
2.3.6 Epidemiology/Pharmacovigilance (Deborah Thompson) :
• The reviewer noted that a pregnancy registry protocol was submitted to
the BLA which she is reviewing to determine if it will be a PMC.
2.3.7 DMPQ (Kathleen Jones, Laura Fontan, Gregory Price, Zhongren Wu, Donald Ertel, Ekaterina Allen, Cheryl Hulme and Iryna Zubkova):
• The DMPQ reviewers are finalizing an IR for the first round of comments
to send to the Applicant next week. The Andover inspections will take place from July 19- 23 and the Puurs inspections occurred from June 23-
July 2. Pending final management review, the waiver for inspec tions of
the Kalamazoo site will be closed next week.
• Until all facilities have been inspected, a firm date for the completion of
DMPQ’s review cannot be provided.
2.3.8 BiMO (Haecin Chun):
• The BIMO reviewers had no issues to share with the review committee.
BIMO inspections were previously conducted for Protocol C4590001.
Due to the COVID -19 pandemic restrictions, no foreign study sites were
selected. On- site inspections were conducted for a total of nine (9)
domes tic study sites and the final classification of all nine inspections
were No Action Indicated (NAI). No significant information was gathered
from the inspections that would preclude approval of the BLA.
• BIMO noted that the data integrity component of these nine inspections
was missing. However, since no study conduct issues were identified during inspections, BIMO does not believe that the lack of the data
integrity component is a concern.
• BIMO wanted to make the team aware of the previous BIMO inspec tion
history of Dr. Michael Levin (Study Site# 1036), who had participated in
FDA-CBER-2021-5683-1024847
STN 1 25742/0 Monthly Meeting date: July 15, 2021
6
the study of Protocol C4590001. His study site was inspected last
November for a Moderna COVID -19 Vaccine clinical trial. At the end of
the inspection, a form 483 was issued. CBE R classified it as OAI (Official
Action Indicated) and an untitled letter was issued to Dr. Levin.
2.3.9 APLB (Oluchi Elekwachi):
• The APLB reviewer reminded the review committee that priority name
review for the submission was completed and comments are being
drafted. If additional safety changes are made, APLB will make an
addendum.
2.3.10 Container Labeling (Daphne Stewart):
• The reviewer noted that no major issued have been identified and minor
IRs will be sent out for the labels later.
2.4 Additional Discussion Item : Post-authorization Effectiveness Data
• N o post -authorization effectiveness data were submitted to the BLA .
However, there have been numerous studies published to date on the real -
world evidence (RWE) from the post-authorization use of Pfizer -BioNTech
COVID- 19 Vaccine. The review team and managers discussed the best way
to include the RWE data into the clinical review memo, if at all.
• The clinical reviewer and others noted that RWE would be difficult to capture
in the review memo due to the high volume of data that is being published;
any information included in the memo would be quickly outdated. As a
compromise, a summary could be included in the review memo stating
whether RWE data affect the conclusions from our review and whether they
are or are not contradictory to what was observed in the clinical trials for effectiveness.
3. Information R equests:
1. 05/18/2021: Three questions regarding datasets (Response in 125742/0.3)
2. 05/20/2021: Four facilities questions and a request for a t -con on 5/25/21 or 5/26/21 to
discuss production schedule and the shutdown activities planned for the Puurs, Belgium site (Response in 125742/0.4)
3. 06/08/2021: Three clinical questions regarding datasets and the PI (Response in
125742/0.6)
4. 06/09/2021: Clinical IR requesting dates for PREA deferred studies (Response in
125742/0.7)
5. 06/25/2021: DBSQC IR regarding the lot release protocol (LRP) template and samples
and reagents (Response in 125742/0.10)
FDA-CBER-2021-5683-1024848
STN 1 25742/0 Monthly Meeting date: July 15, 2021
7
6. 06/25/2021: Clinical IR regarding the document titled “bnt162- 01-intrim3 -report -body”
(Response in 125742/0.9)
7. 06/29/2021: Clinical IR RE latest date of randomization for participants included in the
reactogenicity subset for Study C4591001. (Response in 125742/0.8)
8. 07/02/2021: 18 question from DVP on product related issues and categorical exclusion for an environmental assessment. (Awaiting response)
9. 07/06/2021: Clinical IR RE the document titled “c4591001- interim -mth6 -report -
body.pdf.” (Awaiting response)
10. 07/09/2021:
IR RE the validation of the RNA Integrity by capillary gel electrophoresis
method. (Awaiting response)
11. 07/13/2021: OBE IR to add myocarditis and pericarditis to the PVP. (Awaiting
response)
12. 07/13/2011: DVP IR regarding exception or alternative to the requirement that products in multiple -dose vials include a preservative (Awaiting response)
4. Amendments:
1. 05/18/2021: Second roll and final piece of the BLA, the review clock has started. This
amendment was not submitted in response to an IR.
2. 05/19/2021: Request for Proprietary Name Review. This amendment was not
submitted in response to an IR.
3. 05/19/2021: Response to May 18, 2021, IR RE three dataset questions.
4. 05/24/2021: Response to DMPQ’s May 20, 2021, IR RE four facilities questions and a
request for a t -con on 5/25/21 or 5/26/21 to discuss production schedules and the
shutdown activities planned for the Puurs, Belgium site.
5. 05/24/2021: COVID -19 case strain sequencing data. This amendment was not
submitted in response to an IR.
6. 06/16/2021: Response to June 8, 2021, clinical IR on three clinical questions regarding datasets and the PI.
7. 06/17/2021: Response to June 9, 2021, clinical IR requesting dates for PREA defer red
studies.
8. 07/02/2021: Response to June 29, 2021, clinical IR RE latest date of randomization for
participants included in the reactogenicity subset for Study C4591001.
FDA-CBER-2021-5683-1024849
STN 1 25742/0 Monthly Meeting date: July 15, 2021
8
9. 07/02/2021: Response to June 25, 2021, clinical IR regarding IR regarding the
document titled “bnt162- 01-interim3 -report -body”
10. 07/09/2021: Response to DBSQC’s 6/25/21 IR regarding the lot release protocol (LRP) template and samples & reagents.
5. Post -meeting Updates:
• The Filing Notification Letter was sent to the Applica nt on July 16, 2021.
• The IRs discussed by DBSQC were emailed to the Applicant on July 16, 2021.
• Pfizer submitted STN 125742/ 0.13 on July 19, 2021, waiving their rights to mid - and
late-cycle review meetings.
Appendix Table 3. Review Activities and Target Completion Dates
Task title/description/milestone Target completion date
(Week of…)
BLA submission
Roll 1 submission
Roll 2 submission (final
May 6, 2021
May 18, 2021
Received May 18, 2021
Committee assignment May 19, 2021
First Committee Meeting June 3, 2021
Discussion of testing of DS and DP to support
licensure (DVP and DBSQC) June 4, 2021
Filing review complete June 23, 2021
Request for lot release protocol template, reagents
and samples for testing June 25, 2021
Filing Meeting June 29, 2021
Proprietary Name Review complete July 2, 2021
Reagents and samples received July 9, 2021
Filing Action July 15, 2021
VRBPAC meeting No plan to hold an advisory
committee meeting
Pre-licensure facilities inspections complete July 23, 2021
PeRC briefing materials due July 27, 2021
Post-authorization safety/Epidemiology/
Pharmacovigilance Plan review memo complete August 5, 2021
PeRC meeting August 10, 2021
First set of comments on Package Insert August 11, 2021
Notification of PMC/PMR August 13, 2021
Obtain Lot Release Clearance August 16, 2021
FDA-CBER-2021-5683-1024850
STN 1 25742/0 Monthly Meeting date: July 15, 2021
9
Obtain Compliance check August 16, 2021
Determine non -proprietary name August 16, 2021
APLB review memo complete August 20, 2021
Comments on carton and container labels August 20, 2021
Establishment Inspection Reports complete August 27, 2021
Establish product expiry date August 30, 2021
Nonclinical review memo complete August 30, 2021
DMPQ memo complete (reviewer) August 30, 2021
Waiver for FDA -designated suffix to proper name August 30, 2021
Lot release protocol and testing plan finalized August 30, 2021
CMC review memo complete (reviewer) August 30, 2021
Clinical review memo complete (reviewer) August 30, 2021
Statistical review memo complete (reviewer) August 30, 2021
BIMO review memo complete August 31, 2021
Mid-Cycle Meeting, Internal (scheduled) August 31, 2021
DBSQC review memo complete September 3, 2021
Carton and container labels done September 3, 2021
Labeling review complete September 10, 2021
Mid-Cycle Communication (scheduled) September 13, 2021
(may be canceled)
DMPQ memo complete (supervisory review) September 13, 2021
CMC review memo complete (supervisory review) September 13, 2021
Statistical review memo complete (supervisory
review) September 14, 2021
Clinical review memo complete (supervisory review) September 15, 2021
SBRA complete
(Chair draft: August 30, 2021) September 15, 2021
Target Action Due Date September 15, 2021
DS and DP testing complete (DBSQC) After the ADD
FDA-CBER-2021-5683-1024851